WO2023249480A1 - Oral rinse composition - Google Patents

Oral rinse composition Download PDF

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Publication number
WO2023249480A1
WO2023249480A1 PCT/MY2022/050055 MY2022050055W WO2023249480A1 WO 2023249480 A1 WO2023249480 A1 WO 2023249480A1 MY 2022050055 W MY2022050055 W MY 2022050055W WO 2023249480 A1 WO2023249480 A1 WO 2023249480A1
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WIPO (PCT)
Prior art keywords
oral rinse
rinse composition
composition
volume
amino acids
Prior art date
Application number
PCT/MY2022/050055
Other languages
French (fr)
Inventor
Nur Halimatun Radziah Binti YAHAYA
Original Assignee
Tnh Medicaux Solutions Sdn. Bhd.
Fizidris Mediq Sdn. Bhd.
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
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Publication date
Application filed by Tnh Medicaux Solutions Sdn. Bhd., Fizidris Mediq Sdn. Bhd. filed Critical Tnh Medicaux Solutions Sdn. Bhd.
Priority to PCT/MY2022/050055 priority Critical patent/WO2023249480A1/en
Publication of WO2023249480A1 publication Critical patent/WO2023249480A1/en

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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/12—Antivirals
    • A61P31/14—Antivirals for RNA viruses
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/045—Hydroxy compounds, e.g. alcohols; Salts thereof, e.g. alcoholates
    • A61K31/047—Hydroxy compounds, e.g. alcohols; Salts thereof, e.g. alcoholates having two or more hydroxy groups, e.g. sorbitol
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/13—Amines
    • A61K31/133—Amines having hydroxy groups, e.g. sphingosine
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
    • A61K31/19—Carboxylic acids, e.g. valproic acid
    • A61K31/195—Carboxylic acids, e.g. valproic acid having an amino group
    • A61K31/197—Carboxylic acids, e.g. valproic acid having an amino group the amino and the carboxyl groups being attached to the same acyclic carbon chain, e.g. gamma-aminobutyric acid [GABA], beta-alanine, epsilon-aminocaproic acid, pantothenic acid
    • A61K31/198—Alpha-aminoacids, e.g. alanine, edetic acids [EDTA]
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/21—Esters, e.g. nitroglycerine, selenocyanates
    • A61K31/215—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids
    • A61K31/22—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids of acyclic acids, e.g. pravastatin
    • A61K31/23—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids of acyclic acids, e.g. pravastatin of acids having a carboxyl group bound to a chain of seven or more carbon atoms
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/74—Synthetic polymeric materials
    • A61K31/765—Polymers containing oxygen
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/185—Magnoliopsida (dicotyledons)
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/185—Magnoliopsida (dicotyledons)
    • A61K36/23—Apiaceae or Umbelliferae (Carrot family), e.g. dill, chervil, coriander or cumin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/185—Magnoliopsida (dicotyledons)
    • A61K36/48—Fabaceae or Leguminosae (Pea or Legume family); Caesalpiniaceae; Mimosaceae; Papilionaceae
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/185—Magnoliopsida (dicotyledons)
    • A61K36/53—Lamiaceae or Labiatae (Mint family), e.g. thyme, rosemary or lavender
    • A61K36/534—Mentha (mint)
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/185—Magnoliopsida (dicotyledons)
    • A61K36/73—Rosaceae (Rose family), e.g. strawberry, chokeberry, blackberry, pear or firethorn
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/185—Magnoliopsida (dicotyledons)
    • A61K36/73—Rosaceae (Rose family), e.g. strawberry, chokeberry, blackberry, pear or firethorn
    • A61K36/736—Prunus, e.g. plum, cherry, peach, apricot or almond
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/88—Liliopsida (monocotyledons)
    • A61K36/899—Poaceae or Gramineae (Grass family), e.g. bamboo, corn or sugar cane
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
    • A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
    • A61K47/10—Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
    • A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
    • A61K47/12—Carboxylic acids; Salts or anhydrides thereof
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
    • A61K47/16—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing nitrogen, e.g. nitro-, nitroso-, azo-compounds, nitriles, cyanates
    • A61K47/18—Amines; Amides; Ureas; Quaternary ammonium compounds; Amino acids; Oligopeptides having up to five amino acids
    • A61K47/183—Amino acids, e.g. glycine, EDTA or aspartame
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
    • A61K47/32—Macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. carbomers, poly(meth)acrylates, or polyvinyl pyrrolidone
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/0012—Galenical forms characterised by the site of application
    • A61K9/0053—Mouth and digestive tract, i.e. intraoral and peroral administration
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/10—Dispersions; Emulsions
    • A61K9/107—Emulsions ; Emulsion preconcentrates; Micelles

Definitions

  • the invention relates to an oral rinse composition for the prevention and treatment of respiratory tract infections caused by potentially pathogenic bacteria and viruses.
  • compositions used for oral hygiene typically cleanse the surface of the teeth and other parts inside the mouth.
  • These chemical compositions often available as mouthwash compositions known hitherto generally comprise solutions containing small amounts of colourings, flavourings and antibacterial or other active ingredients. These solutions have found use as breath-freshening, antiseptic and/or anti-plaque mouth rinses or gargle preparations and are commonly used to kill bacteria and other germs that cause bad breath, gingivitis, and plaque.
  • most of the currently available mouthwash compositions are not safe due to its use of harmful chemicals as ingredients and lack of toxicity and broad-spectrum activity against various pathogens such as SARS-CoV-2.
  • Virus particles in respiratory droplets and aerosols generated during medical/dental procedures are a potential source of SARS-CoV-2 cross infection.
  • oral decontamination could be an important adjunct to personal protective equipment and is recommended by several national COVID-19 guidance documents for dental settings.
  • an oral chemical composition which is safe to use and is effective in killing various pathogens such as the SARS-CoV-2 virus.
  • An exemplary oral disinfectant composition is disclosed in the publication titled “In vitro virucidal activity of povidone iodine gargle and mouthwash against SARS-CoV-2: implications for dental practice” by Pouya Hassandarvish et al. published in British Dental Journal (2020).
  • the publication presents a study that tests the product BETADINE Gargle & Mouthwash for virucidal activity at two concentrations - undiluted (PVP- 1 1 % w/v) and at a 50% dilution (PVP-I 0.5% w/v) - for virucidal activity against SARS-CoV- 2 in both clean (0.3 g/l bovine serum albumin [BSA]) and dirty (3.0 g/l BSA + 3 ml/l human erythrocytes) conditions.
  • Virucidal activity of the product, undiluted and at 1 :2 dilution was tested at contact times of 15, 30 and 60 seconds.
  • Viral titres were calculated using the Spearman-Karber method and reported as median tissue culture infectious dose (TCID50/ml).
  • the undiluted product achieved >5 Iog10 reduction in viral titres compared to the control at 15, 30 and 60 seconds under both clean and dirty conditions.
  • the test product demonstrated >4 Iog10 kill at 15 seconds and >5 Iog10 kill at 30 and 60 seconds in both clean and dirty conditions.
  • Another exemplary oral disinfectant composition is disclosed in the publication titled “The Virucidal Efficacy of Oral Rinse Components against SARS-CoV-2 In Vitro” by Evelina et al. in bioRxiv public repository.
  • the publication studies the effectiveness of widely-available mouthwashes to inactivate SARS-CoV-2 in vitro and was tested using a protocol capable of detecting a 5-log10 reduction in infectivity, under conditions mimicking the naso/oropharynx.
  • Nanotechnology is being investigated for its potential in the development of therapeutics, vaccines, diagnostic techniques and strategies to reduce healthcare burden caused by infectious diseases.
  • the aim of the invention is to provide an improved nanotechnology based oral chemical composition which is safe to use and is effective in killing various pathogens such as the SARS-CoV-2 virus.
  • an oral rinse composition comprises: one or more amino acids; one or more plant or fruit extracts; a non-ionic surfactant; an alkanolamine; and a plant based fatty acid; characterized in that virucidal nanomicelle particles are formed by the non-ionic surfactant.
  • the non-ionic surfactant endows nanomicelle properties to the oral rinse composition which has been found to be virucidal and therefore capable of reducing the viral load in saliva in order to help prevent the spread of respiratory viruses.
  • the oral rinse composition further comprising ethylenediaminetetraacetic acid (EDTA), propylene glycol, sodium glycinate, hydrogenated potato starch and linolenic acids.
  • EDTA ethylenediaminetetraacetic acid
  • propylene glycol propylene glycol
  • sodium glycinate sodium glycinate
  • hydrogenated potato starch hydrogenated potato starch and linolenic acids.
  • amino acids are obtained from natural sources.
  • the amino acids in the oral rinse composition are selected from oat amino acids, corn gluten amino acids, apricot kernel amino acids and sodium cocoyl apple amino acids.
  • the plant and fruit extracts in the oral rinse composition are selected from medicago sativa (alfalfa) extract, actinidia arguta fruit extract, daucus carota sativa (carrot) extract and mentha piperita (peppermint) leaf extract.
  • the non-ionic surfactant is poloxamer 184.
  • the hydrophilic head and hydrophobic tail of poloxamer 184 enables the formation of nanomicelle particles.
  • the alkanolamine is ethanolamine.
  • the plant based fatty acid is capric triglyceride.
  • the oral rinse composition when in use for 30 seconds provides >4 Iog10 reduction in virus titre and kills 99.99% SARS-CoV-2 virus.
  • the oral rinse composition when in use kills bacteria and germs that cause bad breath, gingivitis, and plaque.
  • the oral rinse composition in 1 :20 dilution comprises nanomicelle particles with an average size of 5 to 10nm, typically 7.746nm and 80% v/v reverse osmosis (RO) water.
  • nanomicelle particles with an average size of 5 to 10nm, typically 7.746nm and 80% v/v reverse osmosis (RO) water.
  • the oral rinse composition is used as a mouthwash and gargle product.
  • the oral rinse composition further comprises food grade colour and fragrances.
  • the oral rinse composition comprises:
  • EDTA ethylenediaminetetraacetic acid
  • capric triglyceride 1 to 2% by volume capric triglyceride
  • the oral rinse composition is an antibacterial agent effective against pathogenic bacteria and a virucidal agent effective against various types of viruses including SARS-CoV-2 virus.
  • the oral rinse composition further comprises 90% by volume reverse osmosis (RO) water.
  • the oral rinse composition when in use for 30 seconds provides >4 log 10 reduction in virus titre and kills 99.99% SARS-CoV-2 virus.
  • the oral rinse composition when in use kills bacteria and germs that cause bad breath, gingivitis, and plaque.
  • the oral rinse composition is a mouthwash and gargle product.
  • Figure 1 illustrates the average nanomicelle particle size in the oral rinse composition.
  • Figure 2 illustrates the possible mechanism of action of the nanomicelles against viral particles.
  • the present invention relates to an oral rinse composition capable of functioning as a virucidal agent against various types of viruses including SARS-CoV-2 virus.
  • the oral rinse composition is a mouthwash and gargle solution having nanomicelle or micellar properties to function as an antibacterial agent for use against pathogenic bacteria and a virucidal agent against various types of viruses including SARS-CoV-2 virus.
  • the viral load was found highest in the nasopharynx, high in saliva and throat, these areas likely seed the lower respiratory tract and serve as the main reservoirs for droplet transmission and pulmonary disease progression (Maddy et al 2020).
  • gargle solution with virucidal property in achieving viral clearance or interrupting the disease progression (Pattanshetty et al 2020).
  • the oral rinse composition mainly comprises one or more amino acids and one or more plant or fruit extracts.
  • one or more of the amino acids are obtained from natural sources.
  • at least one of the one or more amino acids are selected from natural sources such as, but not limited to, oat amino acids, corn gluten amino acids, apricot kernel amino acids and sodium cocoyl apple amino acids.
  • the plant and fruit extracts in the oral rinse composition are selected from medicago sativa (alfalfa) extract, actinidia arguta fruit extract, daucus carota sativa (carrot) extract and mentha piperita (peppermint) leaf extracts.
  • the oral rinse composition further comprises ethylenediaminetetraacetic acid (EDTA) having a general formula [CH 2 N(CH2CO 2 H)2]2 or the below molecular structure.
  • EDTA ethylenediaminetetraacetic acid
  • the oral rinse composition also comprises compounds such as poloxamer 184 which provides micellar properties to the composition, ethanolamine having a general formula HOCH 2 CH 2 NH 2 , capric triglyceride sourced from natural materials such as coconut oil and glycerine, propylene glycol having a general formula CH 3 CHCH 2 OH and sodium glycinate having a general formula C2H4NNaC>2.
  • the oral rinse composition further comprises food grade colour and fragrances.
  • the oral rinse composition exhibits nanomicelle properties and when used as a mouthwash or gargle solution, the composition functions as a virucidal agent against various types of viruses including SARS-CoV-2 virus.
  • the oral rinse composition when in use for 30 seconds provides >4 Iog10 reduction in virus titre and kills 99.99% SARS-CoV-2 virus.
  • Figure 1 illustrates the average nanomicelle particle size in the oral rinse composition.
  • the oral rinse composition in 1 :20 dilution comprises nanomicelle particles with an average size of 5 to 10nm, typically 7.746nm and 80% v/v reverse osmosis (RO) water functioning as an antibacterial agent for use against pathogenic bacteria and a virucidal agent against various types of viruses including SARS-CoV-2 virus.
  • RO reverse osmosis
  • the oral rinse composition includes constituents such as aqua or water, oat amino acids, corn gluten amino acids, apricot kernel Amino acids, sodium cocoyl apple amino acids, medicago sativa (alfalfa) extract, actinidia arguta fruit extract, daucus carota sativa (carrot) extract, hydrogenated potato starch, linolenic acids, mentha pperita (peppermint) leaf extract, EDTA, poloxamer 184, ethanolamine, capric triglyceride, propylene glycol and sodium glycinate.
  • the oral rinse composition further includes hydrogenated potato starch and linolenic acids as constituents.
  • the constituents such as, but not limited to poloxamer 184 provides nanomicelle properties to the oral rinse composition to function as virucidal agent against viruses including SARS-CoV-2.
  • the principle of action of the oral rinse composition is based on the micellar properties of the constituents such as poloxamer 184 present in the composition.
  • the micellar properties of the constituents cause the formation of an aggregate of surfactant molecules dispersed in a liquid, forming a colloidal suspension.
  • the micellar constituents in the oral rinse composition in the presence of water forms an aggregate with the hydrophilic “head” regions in contact with the surrounding water, sequestering the hydrophobic single-tail regions in the micelle centre. This helps in the disruption, entrapment and subsequent removal or neutralization of viruses, bacteria and other germs that cause bad breath, gingivitis, and plaque.
  • FIG. 2 illustrates the possible mechanism of action of the nanomicelles against viral particles.
  • the oral rinse composition in 1 :20 dilution comprises nanomicelle particles with an average size of 5 to 10nm, typically 7.746nm.
  • the size of the nanomicelle particles are 3 to 4 times smaller than the average size of a SARS-CoV-2 virus (80 to 140nm).
  • SARS-CoV-2 virus 80 to 140nm.
  • the SARS-CoV- 2 virus is encapsulated by a viral envelope comprising a lipid layer.
  • the nanomicelle particles are capable of damaging the virus when their hydrophobic tails wedge themselves into the lipid layer, prying it apart. Apart from that, the nanomicelle particles can also be utilised to deliver drug into the virus.
  • the oral rinse composition comprises about 1 to 2%, typically 1.25% by volume ethylenediaminetetraacetic acid (EDTA), about 1 to 2%, typically 1.25% by volume poloxamer 184, about 1 to 2%, typically 1 .25% by volume ethanolamine, about 1 to 2%, typically 1 .25% by volume capric triglyceride, about 1 to 2%, typically 1 .25% by volume propylene glycol, about 0.1 to 0.5%, typically 0.15% by volume peppermint leaf extract, about 0.1 to 0.5%, typically 0.30% by volume sodium glycinate and about 90%, typically 93.30% water by volume of the composition.
  • EDTA ethylenediaminetetraacetic acid
  • the oral rinse composition thus formed can be effectively used as an antibacterial agent for use against pathogenic bacteria and a virucidal agent against various types of viruses including SARS-CoV-2 virus.
  • the diluted oral rinse composition comprises 93.30% by volume reverse osmosis (RO) water.
  • RO reverse osmosis
  • the oral rinse composition when used as a mouthwash or a gargle solution effectively kills bacteria and other germs that cause bad breath, gingivitis, and plaque.
  • the oral rinse composition when used as a mouthwash or a gargle solution is proven to kill SARS-CoV-2 virus.
  • the efficacy of the oral rinse composition against SARS- CoV-2 virus was tested in-vitro in a suspension assay under two different conditions; dirty condition (3.0 g/l BSA + 3 ml/l erythrocytes interfering substance) and clean condition (0.3 g/l BSA interfering substance); as per the European Standard EN14476 protocol.
  • the oral rinse composition achieved >4 log 10 reduction in virus titre for a 30 second exposure in both clean and dirty conditions.
  • the present oral rinse composition is highly effective against bacteria and viruses such as the SARS-CoV-2 virus in both clean and dirty condition.
  • Table 2 i. Patients with category 1 , 2 and 3 COVID-19 were briefed on the correct procedures of gargling with the oral rinse composition. The patients were instructed to utilise 10ml of the oral rinse composition, tilt their head backward and to gargle for 30 seconds, three times each day for a total of 5 days; ii. Oropharyngeal and nasopharyngeal swabs were taken at day 0 (baseline), 3, 5 and 9 of intervention. The swabs were taken 8 hours after night gargle and before morning gargle and were placed in separate viral transport medium (VTM) bottles. These were subjected to detection of SARS-CoV-2 by real time RT-PCR;
  • VTM viral transport medium
  • Category 2 patients showed a reduction in severity of clinical symptoms such as sore throat, fever, cough and shortness of breath.
  • the oral rinse composition comprises 1-3% by volume ethylenediaminetetraacetic acid (EDTA), 1-3% by volume poloxamer 184, 1-3% by volume ethanolamine, 1-3% by volume capric triglyceride, 1 -3% by volume propylene glycol, 0.1-2% by volume peppermint leaf extract, 0.1 -2% by volume sodium glycinate and water as the rest of the composition.
  • EDTA ethylenediaminetetraacetic acid
  • poloxamer 184 1-3% by volume poloxamer 184
  • ethanolamine 1-3% by volume capric triglyceride
  • propylene glycol 1 -3% by volume propylene glycol
  • peppermint leaf extract 0.1-2% by volume sodium glycinate and water as the rest of the composition.
  • the oral rinse composition thus formed can be effectively used as an antibacterial agent for use against pathogenic bacteria and a virucidal agent against various types of viruses including SARS-CoV-2 virus.
  • the diluted oral rinse composition comprises
  • the oral rinse composition when used as a mouthwash or a gargle solution effectively kills bacteria and other germs that cause bad breath, gingivitis, and plaque.
  • the oral rinse composition can be used as a preventative measure against SARS-CoV-2 virus and for treating preferably low risk patients infected with SARS-CoV-2 virus (asymptomatic and symptomatic).
  • the present oral rinse composition is a non-ionic surfactant compound which complies with OSHA 29 CFR XVI1 1910.1200 Section (i) and contains no hazardous ingredients under current OSHA definition: US EPA/600/4-90/027F USEPA EMSL Protocol for Aquatic Control.
  • This is advantageous as the oral rinse composition can be safely used for gargling and as a mouthwash to effectively kill bacteria and other germs that cause bad breath, gingivitis, and plaque.
  • the use of naturally available compounds for the preparation of the oral rinse composition makes it safe for use by children and people of all categories.
  • the oral rinse composition exhibits nanomicelle properties to function as a virucidal agent against various types of viruses including SARS-CoV-2 virus.

Abstract

An oral rinse composition for the prevention and treatment of respiratory tract infections caused by potentially pathogenic bacteria and viruses. The oral rinse composition when in use as mouthwash and gargle product exhibits nanomicelle properties and is effective against pathogenic bacteria and various types of viruses including SARS-CoV-2.

Description

ORAL RINSE COMPOSITION
Field of Invention
The invention relates to an oral rinse composition for the prevention and treatment of respiratory tract infections caused by potentially pathogenic bacteria and viruses.
Background
With the widespread of infectious diseases at the global level, the use of highly effective and safe disinfectants and cleaning agents has been the primary health challenge around the world. Most of the infectious diseases that are associated with high morbidity and mortality are transmitted through skin contact, through droplets in the air or contact with a colonized surface in the environment. This includes highly resistant bacteria, fungi, viruses (such as the H1 N1 , SARS, SARS-CoV-2 for example) as well as other parasitic pathogens. Unfortunately, the currently widely used disinfectants for personal use and for use in various settings, including hospitals and other places that host high-risk individuals, are marred by several disadvantages, particularly being hazardous in terms of their toxicity, instability and the potential health risks to the users. None of the currently widely used chemical disinfectants is ideal in terms of its safety, lack of toxicity and broad- spectrum activity against various pathogens such as SARS-CoV-2 which caused COVID-19 pandemic.
Chemical compositions used for oral hygiene typically cleanse the surface of the teeth and other parts inside the mouth. These chemical compositions often available as mouthwash compositions known hitherto generally comprise solutions containing small amounts of colourings, flavourings and antibacterial or other active ingredients. These solutions have found use as breath-freshening, antiseptic and/or anti-plaque mouth rinses or gargle preparations and are commonly used to kill bacteria and other germs that cause bad breath, gingivitis, and plaque. However, most of the currently available mouthwash compositions are not safe due to its use of harmful chemicals as ingredients and lack of toxicity and broad-spectrum activity against various pathogens such as SARS-CoV-2. Virus particles in respiratory droplets and aerosols generated during medical/dental procedures are a potential source of SARS-CoV-2 cross infection. In the dental setting, oral decontamination could be an important adjunct to personal protective equipment and is recommended by several national COVID-19 guidance documents for dental settings. Hence there exists a need for an oral chemical composition which is safe to use and is effective in killing various pathogens such as the SARS-CoV-2 virus.
An exemplary oral disinfectant composition is disclosed in the publication titled “In vitro virucidal activity of povidone iodine gargle and mouthwash against SARS-CoV-2: implications for dental practice” by Pouya Hassandarvish et al. published in British Dental Journal (2020). The publication presents a study that tests the product BETADINE Gargle & Mouthwash for virucidal activity at two concentrations - undiluted (PVP- 1 1 % w/v) and at a 50% dilution (PVP-I 0.5% w/v) - for virucidal activity against SARS-CoV- 2 in both clean (0.3 g/l bovine serum albumin [BSA]) and dirty (3.0 g/l BSA + 3 ml/l human erythrocytes) conditions. Virucidal activity of the product, undiluted and at 1 :2 dilution, was tested at contact times of 15, 30 and 60 seconds. Viral titres were calculated using the Spearman-Karber method and reported as median tissue culture infectious dose (TCID50/ml). The undiluted product achieved >5 Iog10 reduction in viral titres compared to the control at 15, 30 and 60 seconds under both clean and dirty conditions. At a twofold dilution (0.5% PVP-I), the test product demonstrated >4 Iog10 kill at 15 seconds and >5 Iog10 kill at 30 and 60 seconds in both clean and dirty conditions.
Another exemplary oral disinfectant composition is disclosed in the publication titled “The Virucidal Efficacy of Oral Rinse Components Against SARS-CoV-2 In Vitro” by Evelina et al. in bioRxiv public repository. The publication studies the effectiveness of widely-available mouthwashes to inactivate SARS-CoV-2 in vitro and was tested using a protocol capable of detecting a 5-log10 reduction in infectivity, under conditions mimicking the naso/oropharynx. During a 30 second exposure, two rinses containing cetylpyridinium chloride and a third with ethanol/ethyl lauroyl arginate eliminated live virus to EN14476 standards (>4-log10 reduction), while others with ethanol/essential oils and povidone-iodine (PVP-I) eliminated virus by 2-3-log10. Chlorhexidine or ethanol alone had little or no ability to inactivate virus in this assay. Studies are warranted to determine whether these formulations can inactivate virus in the human oropharynx in vivo, and whether this might impact transmission. The study identified three products which contained either (i) 0.07-0.1 % CPC (Dentyl Dual Action, Dentyl Fresh Protect) or (ii) 23 % ethanol with LAE (Listerine Advanced) provided the greatest level of inactivation against SARS-CoV-2 virus.
Nanotechnology is being investigated for its potential in the development of therapeutics, vaccines, diagnostic techniques and strategies to reduce healthcare burden caused by infectious diseases. Thus the aim of the invention is to provide an improved nanotechnology based oral chemical composition which is safe to use and is effective in killing various pathogens such as the SARS-CoV-2 virus.
Summary of Invention
In an aspect of the invention, an oral rinse composition is disclosed. The oral rinse composition comprises: one or more amino acids; one or more plant or fruit extracts; a non-ionic surfactant; an alkanolamine; and a plant based fatty acid; characterized in that virucidal nanomicelle particles are formed by the non-ionic surfactant.
Advantageously, the non-ionic surfactant endows nanomicelle properties to the oral rinse composition which has been found to be virucidal and therefore capable of reducing the viral load in saliva in order to help prevent the spread of respiratory viruses.
In one embodiment, the oral rinse composition further comprising ethylenediaminetetraacetic acid (EDTA), propylene glycol, sodium glycinate, hydrogenated potato starch and linolenic acids.
In yet another embodiment, the amino acids are obtained from natural sources.
In one instance, the amino acids in the oral rinse composition are selected from oat amino acids, corn gluten amino acids, apricot kernel amino acids and sodium cocoyl apple amino acids.
In another embodiment, the plant and fruit extracts in the oral rinse composition are selected from medicago sativa (alfalfa) extract, actinidia arguta fruit extract, daucus carota sativa (carrot) extract and mentha piperita (peppermint) leaf extract.
In one embodiment, the non-ionic surfactant is poloxamer 184. Advantageously, the hydrophilic head and hydrophobic tail of poloxamer 184 enables the formation of nanomicelle particles.
In one embodiment, the alkanolamine is ethanolamine.
In one embodiment, the plant based fatty acid is capric triglyceride.
In one embodiment, the oral rinse composition when in use for 30 seconds provides >4 Iog10 reduction in virus titre and kills 99.99% SARS-CoV-2 virus.
The oral rinse composition when in use kills bacteria and germs that cause bad breath, gingivitis, and plaque.
In one instance, the oral rinse composition in 1 :20 dilution comprises nanomicelle particles with an average size of 5 to 10nm, typically 7.746nm and 80% v/v reverse osmosis (RO) water.
In one embodiment, the oral rinse composition is used as a mouthwash and gargle product.
In one embodiment, the oral rinse composition further comprises food grade colour and fragrances.
According to an alternate embodiment, the oral rinse composition comprises:
1 to 2% by volume ethylenediaminetetraacetic acid (EDTA);
1 to 2% by volume poloxamer 184;
1 to 2% by volume ethanolamine;
1 to 2% by volume capric triglyceride;
1 to 2% by volume propylene glycol;
0.1 to 0.5% by volume peppermint leaf extract; and
0.1 to 0.5% by volume sodium glycinate.
According to said alternate embodiment, the oral rinse composition is an antibacterial agent effective against pathogenic bacteria and a virucidal agent effective against various types of viruses including SARS-CoV-2 virus. According to said alternate embodiment, the oral rinse composition further comprises 90% by volume reverse osmosis (RO) water.
According to said alternate embodiment, the oral rinse composition when in use for 30 seconds provides >4 log 10 reduction in virus titre and kills 99.99% SARS-CoV-2 virus.
According to said alternate embodiment, the oral rinse composition when in use kills bacteria and germs that cause bad breath, gingivitis, and plaque.
The oral rinse composition, according to said alternate embodiment, is a mouthwash and gargle product.
Brief Description of the Drawings
Figure 1 illustrates the average nanomicelle particle size in the oral rinse composition.
Figure 2 illustrates the possible mechanism of action of the nanomicelles against viral particles.
Detailed Description
The present invention relates to an oral rinse composition capable of functioning as a virucidal agent against various types of viruses including SARS-CoV-2 virus. According to a preferred embodiment, the oral rinse composition is a mouthwash and gargle solution having nanomicelle or micellar properties to function as an antibacterial agent for use against pathogenic bacteria and a virucidal agent against various types of viruses including SARS-CoV-2 virus. As the viral load was found highest in the nasopharynx, high in saliva and throat, these areas likely seed the lower respiratory tract and serve as the main reservoirs for droplet transmission and pulmonary disease progression (Maddy et al 2020). Considering the pathogenesis of SARS-CoV-2 virus, there is a role of gargle solution with virucidal property in achieving viral clearance or interrupting the disease progression (Pattanshetty et al 2020).
According to an embodiment, the oral rinse composition mainly comprises one or more amino acids and one or more plant or fruit extracts. In one instance, one or more of the amino acids are obtained from natural sources. In a yet another embodiment, at least one of the one or more amino acids are selected from natural sources such as, but not limited to, oat amino acids, corn gluten amino acids, apricot kernel amino acids and sodium cocoyl apple amino acids. In one embodiment, the plant and fruit extracts in the oral rinse composition are selected from medicago sativa (alfalfa) extract, actinidia arguta fruit extract, daucus carota sativa (carrot) extract and mentha piperita (peppermint) leaf extracts.
According to said embodiment, the oral rinse composition further comprises ethylenediaminetetraacetic acid (EDTA) having a general formula [CH2N(CH2CO2H)2]2 or the below molecular structure.
Figure imgf000008_0001
The oral rinse composition also comprises compounds such as poloxamer 184 which provides micellar properties to the composition, ethanolamine having a general formula HOCH2CH2NH2, capric triglyceride sourced from natural materials such as coconut oil and glycerine, propylene glycol having a general formula CH3CHCH2OH and sodium glycinate having a general formula C2H4NNaC>2. The oral rinse composition further comprises food grade colour and fragrances. The oral rinse composition exhibits nanomicelle properties and when used as a mouthwash or gargle solution, the composition functions as a virucidal agent against various types of viruses including SARS-CoV-2 virus. The oral rinse composition when in use for 30 seconds provides >4 Iog10 reduction in virus titre and kills 99.99% SARS-CoV-2 virus.
Figure 1 illustrates the average nanomicelle particle size in the oral rinse composition. The oral rinse composition in 1 :20 dilution comprises nanomicelle particles with an average size of 5 to 10nm, typically 7.746nm and 80% v/v reverse osmosis (RO) water functioning as an antibacterial agent for use against pathogenic bacteria and a virucidal agent against various types of viruses including SARS-CoV-2 virus.
In another embodiment, the oral rinse composition includes constituents such as aqua or water, oat amino acids, corn gluten amino acids, apricot kernel Amino acids, sodium cocoyl apple amino acids, medicago sativa (alfalfa) extract, actinidia arguta fruit extract, daucus carota sativa (carrot) extract, hydrogenated potato starch, linolenic acids, mentha pperita (peppermint) leaf extract, EDTA, poloxamer 184, ethanolamine, capric triglyceride, propylene glycol and sodium glycinate. In one embodiment, the oral rinse composition further includes hydrogenated potato starch and linolenic acids as constituents. The constituents such as, but not limited to poloxamer 184 provides nanomicelle properties to the oral rinse composition to function as virucidal agent against viruses including SARS-CoV-2.
The principle of action of the oral rinse composition is based on the micellar properties of the constituents such as poloxamer 184 present in the composition. The micellar properties of the constituents cause the formation of an aggregate of surfactant molecules dispersed in a liquid, forming a colloidal suspension. The micellar constituents in the oral rinse composition in the presence of water forms an aggregate with the hydrophilic “head” regions in contact with the surrounding water, sequestering the hydrophobic single-tail regions in the micelle centre. This helps in the disruption, entrapment and subsequent removal or neutralization of viruses, bacteria and other germs that cause bad breath, gingivitis, and plaque.
Figure 2 illustrates the possible mechanism of action of the nanomicelles against viral particles. The oral rinse composition in 1 :20 dilution comprises nanomicelle particles with an average size of 5 to 10nm, typically 7.746nm. The size of the nanomicelle particles are 3 to 4 times smaller than the average size of a SARS-CoV-2 virus (80 to 140nm). This enables the nanomicelle particles to disrupt and damage the virus by blocking surface receptors, interfering with cell docking/attachment, causing damage to the virus envelope and damaging the virus RNA. Studies show that the SARS-CoV- 2 virus is encapsulated by a viral envelope comprising a lipid layer. The nanomicelle particles are capable of damaging the virus when their hydrophobic tails wedge themselves into the lipid layer, prying it apart. Apart from that, the nanomicelle particles can also be utilised to deliver drug into the virus.
In yet another embodiment, the oral rinse composition comprises about 1 to 2%, typically 1.25% by volume ethylenediaminetetraacetic acid (EDTA), about 1 to 2%, typically 1.25% by volume poloxamer 184, about 1 to 2%, typically 1 .25% by volume ethanolamine, about 1 to 2%, typically 1 .25% by volume capric triglyceride, about 1 to 2%, typically 1 .25% by volume propylene glycol, about 0.1 to 0.5%, typically 0.15% by volume peppermint leaf extract, about 0.1 to 0.5%, typically 0.30% by volume sodium glycinate and about 90%, typically 93.30% water by volume of the composition. The oral rinse composition thus formed can be effectively used as an antibacterial agent for use against pathogenic bacteria and a virucidal agent against various types of viruses including SARS-CoV-2 virus. In one instance, the diluted oral rinse composition comprises 93.30% by volume reverse osmosis (RO) water. The oral rinse composition when used as a mouthwash or a gargle solution effectively kills bacteria and other germs that cause bad breath, gingivitis, and plaque.
The oral rinse composition when used as a mouthwash or a gargle solution is proven to kill SARS-CoV-2 virus. The efficacy of the oral rinse composition against SARS- CoV-2 virus was tested in-vitro in a suspension assay under two different conditions; dirty condition (3.0 g/l BSA + 3 ml/l erythrocytes interfering substance) and clean condition (0.3 g/l BSA interfering substance); as per the European Standard EN14476 protocol. The oral rinse composition achieved >4 log 10 reduction in virus titre for a 30 second exposure in both clean and dirty conditions. These findings suggest that the oral rinse composition can kill 99.99% SARS-CoV-2 virus in 30 seconds. The below table, Table 1 , compares the reduction in virus titres in clean and dirty conditions at 30s and 60s contact time.
Figure imgf000010_0001
Table 1
From Table 1 , it is evident that the reduction in virus titre of >4 Iog10 in clean and dirty conditions corresponds to a virus inactivation of > 99.99%. Thus, the present oral rinse composition is highly effective against bacteria and viruses such as the SARS-CoV-2 virus in both clean and dirty condition.
The efficacy of the oral rinse composition against SARS-CoV-2 virus was also tested in patients with COVID-19 (coronavirus disease) according to the protocol below. COVID-19 patients in Malaysia are classified into 5 categories as stated in Table 2.
Figure imgf000010_0002
Figure imgf000011_0001
Table 2 i. Patients with category 1 , 2 and 3 COVID-19 were briefed on the correct procedures of gargling with the oral rinse composition. The patients were instructed to utilise 10ml of the oral rinse composition, tilt their head backward and to gargle for 30 seconds, three times each day for a total of 5 days; ii. Oropharyngeal and nasopharyngeal swabs were taken at day 0 (baseline), 3, 5 and 9 of intervention. The swabs were taken 8 hours after night gargle and before morning gargle and were placed in separate viral transport medium (VTM) bottles. These were subjected to detection of SARS-CoV-2 by real time RT-PCR;
Hi. Patients were also given a diary to record their gargling practice and symptoms (if any) during the intervention period; iv. Clinical data collection sheets were provided to the attending clinicians. The required information included demographic data, daily vital signs, serial absolute lymphocytic count, CRP, chest radiograph and symptoms. Clinical monitoring was conducted until the patients were discharged.
Said protocol has been accepted by main professional dental associations worldwide, such as the American Dental Association (ADA, 2020).
From the implementation of the protocol above, it was observed that category 1 patients showed a reduction in clinical symptoms and with consistent usage of the oral rinse composition 3 times a day, they exhibited no further severe symptoms and were able to continue their daily activities after completing the required quarantine time.
Category 2 patients showed a reduction in severity of clinical symptoms such as sore throat, fever, cough and shortness of breath.
There was a significant reduction in the saliva viral load at both 5 and 60 minutes after rinsing with the oral rinse composition compared to the control group (patients with category 1 , 2 and 3 COVID-19 who did not observe the protocol).
In a yet another embodiment, the oral rinse composition comprises 1-3% by volume ethylenediaminetetraacetic acid (EDTA), 1-3% by volume poloxamer 184, 1-3% by volume ethanolamine, 1-3% by volume capric triglyceride, 1 -3% by volume propylene glycol, 0.1-2% by volume peppermint leaf extract, 0.1 -2% by volume sodium glycinate and water as the rest of the composition. The oral rinse composition thus formed can be effectively used as an antibacterial agent for use against pathogenic bacteria and a virucidal agent against various types of viruses including SARS-CoV-2 virus. In one instance, the diluted oral rinse composition comprises 80-95% by volume reverse osmosis (RO) water. The oral rinse composition when used as a mouthwash or a gargle solution effectively kills bacteria and other germs that cause bad breath, gingivitis, and plaque. The oral rinse composition can be used as a preventative measure against SARS-CoV-2 virus and for treating preferably low risk patients infected with SARS-CoV-2 virus (asymptomatic and symptomatic).
The present oral rinse composition is a non-ionic surfactant compound which complies with OSHA 29 CFR XVI1 1910.1200 Section (i) and contains no hazardous ingredients under current OSHA definition: US EPA/600/4-90/027F USEPA EMSL Protocol for Aquatic Control. This is advantageous as the oral rinse composition can be safely used for gargling and as a mouthwash to effectively kill bacteria and other germs that cause bad breath, gingivitis, and plaque. The use of naturally available compounds for the preparation of the oral rinse composition makes it safe for use by children and people of all categories. Further, the oral rinse composition exhibits nanomicelle properties to function as a virucidal agent against various types of viruses including SARS-CoV-2 virus.

Claims

1. An oral rinse composition comprising: one or more amino acids; one or more plant or fruit extracts; a non-ionic surfactant; an alkanolamine; and a plant based fatty acid; characterized in that virucidal nanomicelle particles are formed by the non-ionic surfactant.
2. The oral rinse composition of claim 1 further comprising ethylenediaminetetraacetic acid (EDTA), propylene glycol, sodium glycinate, hydrogenated potato starch and linolenic acids.
3. The oral rinse composition of claim 1 wherein at least one of the one or more amino acids are selected from oat amino acids, corn gluten amino acids, apricot kernel amino acids and sodium cocoyl apple amino acids.
4. The oral rinse composition of claim 1 wherein at least one of the one or more plant and fruit extracts are selected from medicago sativa (alfalfa) extract, actinidia arguta fruit extract, daucus carota sativa (carrot) extract and mentha piperita (peppermint) leaf extract.
5. The oral rinse composition of claim 1 wherein the non-ionic surfactant is poloxamer 184.
6. The oral rinse composition of claim 1 wherein the alkanolamine is ethanolamine.
7. The oral rinse composition of claim 1 wherein the plant based fatty acid is capric triglyceride.
8. The oral rinse composition of claim 1 wherein the composition in 1 :20 dilution comprises nanomicelle particles with an average size of 5 to 10 nm and 80% v/v reverse osmosis (RO) water.
9. An oral rinse composition comprising:
1 to 2% by volume ethylenediaminetetraacetic acid (EDTA);
1 to 2% by volume poloxamer 184;
1 to 2% by volume ethanolamine;
1 to 2% by volume capric triglyceride;
1 to 2% by volume propylene glycol;
0.1 to 0.5% by volume peppermint leaf extract; and
0.1 to 0.5% by volume sodium glycinate; characterized in that the oral rinse composition is an antibacterial agent effective against pathogenic bacteria and a virucidal agent effective against various types of viruses including SARS-CoV-2 virus.
10. The oral rinse composition of claim 9 wherein the composition further comprises 90% by volume reverse osmosis (RO) water.
11. The oral rinse composition of any preceding claim wherein the composition when in use for 30 seconds provides >4 log 10 reduction in virus titre and kills 99.99% SARS-CoV-2 virus.
12. The oral rinse composition of any preceding claim wherein the composition when in use kills bacteria and germs that cause bad breath, gingivitis, and plaque.
13. The oral rinse composition of any preceding claim wherein the oral rinse composition is a mouthwash and gargle product.
PCT/MY2022/050055 2022-06-21 2022-06-21 Oral rinse composition WO2023249480A1 (en)

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Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2003000243A1 (en) * 2001-06-25 2003-01-03 The Regents Of The University Of Michigan Antimicrobial nanoemulsion compositions and methods
US20030194445A1 (en) * 2001-11-12 2003-10-16 Kuhner Carla H. Compositions and methods of use of peptides in combination with biocides and/or germicides
WO2014195872A1 (en) * 2013-06-04 2014-12-11 Vyome Biosciences Pvt. Ltd. Coated particles and compositions comprising same

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2003000243A1 (en) * 2001-06-25 2003-01-03 The Regents Of The University Of Michigan Antimicrobial nanoemulsion compositions and methods
US20030194445A1 (en) * 2001-11-12 2003-10-16 Kuhner Carla H. Compositions and methods of use of peptides in combination with biocides and/or germicides
WO2014195872A1 (en) * 2013-06-04 2014-12-11 Vyome Biosciences Pvt. Ltd. Coated particles and compositions comprising same

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